Alterations of the mitochondrial enzyme, monoamine oxidase (MAO), in brain has been implicated in the etiology of a variety of behavioral disorders including schizophrenia and uni- and bipolar depression. Accordingly, the project in my laboratory has as its objectives to (1) characterize the properties of human brain type A and B MAO and to (2) understand the effects of drugs and hormones on these isoenzymes. To date, we have extensively studied the kinetic properties of the B form of the human brain MAO. The reaction sequence proceeds via a double-displacement mechanism which can account for many of the unique features of this enzyme in relation to drug binding and inhibition and in reference to a variety of other biochemical parameters. Other studies have demonstrated that both the tricyclic antidepressant and the structurally similar antipsychotic drugs (phenothiazines) inhibit both the A and B forms of human brain MAO at concentrations found in vivo in brain. In addition, we have also examined the effect of progesterone administered pre- and postnatally to female rats on MAO activity in brains of rat fetuses and newborns. Results of these studies reveal that progesterone increases both MAO A and B activity both in utero and after parturition. Since behavioral changes have been reported to be associated with progesterone administration to the developing fetus, our studies suggest that these behavioral effects may be caused, at least in part, by alteration in brain MAO activity.